This invention relates in general to orally administered, slow release compositions and more particularly to a relatively dense sustained release composition for ruminant animals that permits a predicted and controlled release of medicaments and the process for manufacturing the same.
Several sustained release bolus preparations are available to veterinary medical personnel but many do not enjoy widespread commercial use. These sustained release dosage forms are used for oral administration of therapeutic substances to ruminants such as cattle, sheep and goats. The physical shape of these sustained release dosage forms is in the form of a bolus that is dense and heavy enough to be retained in the rumeno-reticular sac for long periods of time while the therapeutically active substance is slowly released by disintegration of the boluses and granules within the rumeno-reticular sac. However, the release of the therapeutically active substance from the bolus is unpredictable and not controllable. A portion of the therapeutically active substance is released in the rumen where it is exposed to ruminal bacteria which can inactivate the therapeutically active substance. Additionally, the microbes in the rumen can also be rendered ineffective and disturb the normal digestive fermentation process in the rumen. This, of course, is undesirable, and there is a definite need for a sustained release bolus to have a predictable and controllable release of a therapeutically active substance so that it is not inactivated in the rumen or disruptive of the normal digestive process in a ruminant.
U.S. Pat. No. 3,056,724 discloses pellets for administration to ruminants which provide biologically active substances to the animal's alimentary tract over extended periods of time. The disclosure states that trace elements in pellet form may stay in the animal for an excess of one year, whereas therapeutic substances, such as sulfonamide or antibiotic medication will last for about three months or so. However, a pellet form for administration of a therapeutically active substance that may be utilized for a short period of time is not disclosed. The need for a slow release short term bolus arises in food producing ruminants, for any medication given to the animal must be clear of its tissues before the animal is slaughtered.
U.S. Pat. No. 3,507,952 describes a bolus containing a therapeutically active substance combined with a filler and a critical lubricant. The bolus supplies the therapeutically active substance to the ruminant for short periods of time in minimal dosage levels. As a practical matter, the bolus has minimal and inadequate effects on acute and chronic diseases of ruminants.
The present invention relates to an improvement in the control of disintegration of veterinary boluses in ruminant animals, with said boluses releasing a therapeutically active substance for a period of up to about 15 days in duration.
We have found that by the process of this invention controlled release veterinary boluses for relatively short term therapeutic effects can be prepared with a vegetable proteinaceous material which has never before been recognized as a critical ingredient in the manufacture of a controlled release composition. This critical ingredient is zein, which possesses unique solubility characteristics significantly different from conventional binding agents and disintegrants. Zein when used in the process of the present invention serves a multiple purpose: a portion of zein is utilized as a controlled release agent which facilitates the gradual breakdown of the bolus to granules in the rumeno reticular sac and zein is also utilized as a granulation binder to (a) protect the active ingredients, such as antibacterials in the granules until they are carried to the intestine where the active ingredient is released; (b) protect the vital essential microorganisms normally responsible for digestive fermentation within the rumen from being adversely affected by the therapeutically active ingredient, particularly, antibacterials, such as sulfonamides and antibiotics. This multiple action of the vegetable proteinaceous material, particularly the action wherein the bolus is broken down into granules, provides for the dispensing of medicaments to ruminants for relatively short periods of time without frequent oral administration of the medicament. The method and composition of this invention therefore obviates the prior art disadvantages of unpredictable release, long term effect, harmful effects on ruminal microorganisms and inadequately maintained blood levels of therapeutically active substances, particularly antibacterials such as sulfonamides, by simplifying the prior art procedure to fill a commercial need for a bolus with a relatively short term effect, for example, up to about 15 days.